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Pregnancy-associated genes contribute to antiluteolytic mechanisms in ovine coprus luteum

ABSTRACT: Ovine interferon-tau (IFNT) is released from the conceptus by Day 12 of pregnancy and disrupts pulsatile release of endometrial prostaglandin F2 alpha (PGF), thereby protecting the corpus luteum (CL). IFNT may also have endocrine action through inducing interferon stimulated genes (ISGs) in the CL. The hypothesis that gene expression differs in CL collected from pregnant (P) and non-pregnant (NP) ewes by Day 14 due to the lytic action of PGF during the estrous cycle or the presence of a conceptus was tested. RNA was isolated on Days 12 and 14 in NP or P ewes (n = 3 ewes/group) and analyzed using the Affymetrix bovine microarray (24,000 targets). Differential gene expression (>1.5 fold, P < 0.05) was confirmed using semi-quantitative real time PCR (RTPCR). Serum progesterone concentrations decreased (P < 0.05) from 1.7 ng/ml on Day 12 to 1.3 ng/ml by Day 14 in NP ewes suggesting initiation of luteolysis; and remained > 1.7 ng/ml in Day 12 and 14 P ewes indicating that the conceptus protected the CL from luteolysis. Early luteolysis from Day 12 to 14 NP was associated with differential expression of 683 genes, including SERPINE1 and THBS1. Presence of a conceptus from Day 12 to 14 also induced expression of 743 genes, i.e., ISGs (ISG15, MX1), PTX3, and IL-6 and stabilized expression of VEGF and LHR genes. In conclusion, pregnancy circumvents luteolytic pathways, and activates or stabilizes genes associated with interferon, chemokine, cell adhesion, cytoskeletal, angiogenic and epithelial to mesynchymal transition pathways in the CL.

ORGANISM(S): Bos taurus Ovis aries

PROVIDER: GSE47776 | GEO | 2013/11/01

SECONDARY ACCESSION(S): PRJNA207799

REPOSITORIES: GEO

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Project description:Interferon tau (IFNT), a Type I IFN similar to alpha IFNs (IFNA), is the pregnancy recognition signal, produced by the ruminant conceptus. To elucidate specific effects of bovine IFNT and of other conceptus-derived factors, endometrial gene expression changes during early pregnancy were compared to gene expression changes after intrauterine application of human IFNA2. In study one, endometrial tissue samples were obtained on days (D) 12, 15, and 18 post-mating from nonpregnant or pregnant heifers. In study two, heifers were treated from D14 to D16 of the estrous cycle with an intrauterine device releasing IFNA2 or placebo lipid extrudates or PBS only as controls. Endometrial biopsies were collected after flushing the uterus. All samples from both experiments were analyzed with an Affymetrix Bovine Genome Array. Study one revealed differential gene expression between pregnant and nonpregnant endometria on D15 and D18. In study two, IFNA2 treatment resulted in differential gene expression in the bovine endometrium. Comparison of the datasets from both studies identified genes that were differentially expressed in response to IFNA2 but not in response to pregnancy on D15 or D18. Vice versa, genes were found as differentially expressed during pregnancy but not after IFNA2 treatment. In study three, spatiotemporal alterations in expression of selected genes were determined in uteri from nonpregnant and early pregnant heifers using in situ hybridization. The findings of this study suggest differential effects of bovine IFNT compared to human IFNA2 and that some pregnancy-specific changes in the endometrium are elicited by conceptus-derived factors other than IFNT. Study I: Early pregnancy; day 12 of pregnancy (n=5 heifers), day 15 of pregnancy (n=3), day 18 of pregnancy (n=4), day 12 cyclic controls (n=5), day 15 cyclic controls (n=3), day 18 cyclic controls (n=4). Study II: Treatment with human interferon alpha (IFNA); IFNA treatment group (IFNA, n=3 heifers), placebo group (PLAC, n=3 heifers), control group (CONT, n=3 heifers).

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Pregnancy-associated genes contribute to antiluteolytic mechanisms in ovine coprus luteum

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